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Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite

Abstract

As the malaria parasite, Plasmodium falciparum, grows within its host erythrocyte it induces an increase in the permeability of the erythrocyte membrane to a range of low-molecular-mass solutes, including Na+ and K+ (ref. 1). This results in a progressive increase in the concentration of Na+ in the erythrocyte cytosol2,3. The parasite cytosol has a relatively low Na+ concentration2,4 and there is therefore a large inward Na+ gradient across the parasite plasma membrane. Here we show that the parasite exploits the Na+ electrochemical gradient to energize the uptake of inorganic phosphate (Pi), an essential nutrient. Pi was taken up into the intracellular parasite by a Na+-dependent transporter, with a stoichiometry of 2Na+:1Pi and with an apparent preference for the monovalent over the divalent form of Pi. A Pi transporter (PfPiT) belonging to the PiT family was cloned from the parasite and localized to the parasite surface. Expression of PfPiT in Xenopus oocytes resulted in Na+-dependent Pi uptake with characteristics similar to those observed for Pi uptake in the parasite. This study provides new insight into the significance of the malaria-parasite-induced alteration of the ionic composition of its host cell.

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Figure 1: P i transport in malaria parasites ‘isolated’ from their host erythrocytes by permeabilization with saponin.
Figure 2: The P. falciparum P i transporter, PfPiT.
Figure 3: Transport characteristics of PfPiT in Xenopus oocytes.

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Acknowledgements

We thank the Australian Red Cross Blood Service (Canberra and Melbourne) for the provision of blood. This work was supported by grants from the Australian National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), the Howard Hughes Medical Institute and the ARC/NHMRC Network for Parasitology. Author Contributions S.B. and K.K. contributed equally to this work and are joint senior authors.

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Correspondence to Kiaran Kirk.

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Saliba, K., Martin, R., Bröer, A. et al. Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite. Nature 443, 582–585 (2006). https://doi.org/10.1038/nature05149

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